Angioplasty is a popular method of treating coronary artery disease without the dangers of surgery and anesthesia. However, the results range from excellent to disappointing. Therefore, there is a need to develop a new method of obtaining data on the lesion being treated which will aid in correlating the disease to the outcome of the treatment. Eventually this could provide guidance in patient selection, and in follow-on therapy that would make angioplasty more successful.
Vascular disease is the largest cause of death in this country. Vascular disease, which has as its end stage complete occlusion of the affected vessels, can cause stroke, heart attack, kidney failure or loss of limb in affected patients. New techniques are required to evaluate vascular disease and enhance our ability to study this problem, thereby allowing more effective diagnosis and permitting therapies to be administered safely Specifically, new methodologies are required to analyze the thickness of the vessel wall, the nature of the vessel wall, the integrity of the lining of the vessel, and to evaluate the presence of intraluminal thrombosis or atherosclerotic debris. Vascular disease is primarily caused by the development of a atherosclerotic plaque. As the plaque increases in size, there is either an eccentric or concentric disposition of atheromatoses in the vessel. With an encroachment of plaque on the vascular lumen, there is a restriction of blood flow through the vessel. At first this flow restriction occurs only during periods when increased flow is required. For example, even when there is a blockage in the arteries leading to the legs there is normal blood flow at rest, however, when walking, an increased blood flow is required. Pain will thus occur only during walking when the blockage in the vessel prevents the needed increase in flow through the narrowed blood vessel. As plaque development progresses, there may be further encroachment into the lumen of the vessel and a decrease in flow at rest may occur. Pathologic changes in the plaque such as splitting or lifting up of the plaque may initiate the formation of a thrombus which may then cause complete occlusion of the vessel. Such complete occlusion will then cause death in the tissue normally supplied by that vessel. For example, if the vessel is one of the heart's vessels, a heart attack will occur, or if the vessel is one leading to the brain, a stroke will occur. Although in the past little could be done to treat these problems, in recent years new therapeutic interventions have evolved. These include surgical removal of the plaque, bypass of the plaque, and balloon angioplasty in which a small balloon catheter is positioned across the stenosis and then inflated to crush the blockage. In addition, newer technologies are being developed including ablation of the plaque by a laser beam or removal of the plaque by miniaturized mechanical devices. Recently, Barry et al have suggested that radiofrequency generated thermal energy can have a substantial effect on the mechanical and histologic characteristics of the arterial wall, and may have implications for radiofrequency angioplasty. American Heart Journal, pages 332-341 (February 1989).
Most current vascular angiography techniques permit visualization only of the diameter of the vessel. Visualization of the entire vascular wall is not possible. Many devices and approaches have been suggested for such imaging of the human vasculature. Perhaps the most common approach relies upon intravenous injection of contrast media in combination with imaging from an external source. More recently, attention has been directed to imaging the walls of vessels to determine their thicknesses, particularly in relation to whether plaque growth has narrowed the lumen of a coronary artery such that treatment by angioplasty and/or by-pass is recommended.
There is, of course, a great need to accurately diagnose the condition of arteries such as the coronary arteries, and to do so in real time. Imaging of plaques is somewhat complicated in that not all plaques are calcified, and may not be imaged by certain imaging techniques. Such deficiencies in diagnostic visualization limit the knowledge of vascular pathology and hence, the understanding of the development and course of the disease process. In addition, selection of therapeutic interventions may be hindered because of these limitations. Currently, there is a 30% incidence of recurrence of stenosis following coronary balloon angioplasty. The process of restenosis is poorly understood. Investigation in the vascular wall may shed light on the mechanisms and course of such recurrence of such stenosis.
Full visualization of the vessel wall would also assist in understanding the base line anatomy and physiology of the vessel. Visualization is also needed to plan proposed therapeutic interventions and to determine the results of such interventions. Such visualization of the vessel should provide as close an approximation to the histologic cross section of the vessel as possible. Such a cross section should include delineation of the lumen of the vessel, any intraluminal masses or thrombosis, any tear in the wall in the vessel and delineation of the thickness of the vessel wall and the presence of calcium in the vessel wall.
An advantage of ultrasonic imaging is that relatively soft tissues can be imaged effectively, although the depth of imaging is somewhat limited. It has not proven to be possible, for example, to use external transducers to image coronary arteries of closed chest patients. On the other hand, were ultrasonic imaging possible in closed chest patients, it might be possible to locate soft tissue lesions and areas of uncalcified plaque which presently escape other diagnostic techniques.
Accordingly, it has been suggested to provide an ultrasonic probe or transducer to image the walls of vessels such as the coronary artery to determine whether undesirable thickening is present. In order to be effective, however, such probes must be miniaturized to diameters which will permit transcutaneous insertions into the vessel lumen. Additionally, such probes must exhibit sufficient flexibility to allow the required intravascular maneuvering to the target site.
Various investigators have suggested designs for ultrasonic imaging catheters. Some of these are intended merely to determine the volume or rate of flow of blood through the vessel lumen. U.S. Pat. No. 4,589,419 (Laughlin et al), U.S. Pat. No. 4,637,401 (Johnston), and U.S. Pat. No. 4,665,925 (Millar) disclose catheters using ultrasonic transducers to determine blood flow. In this regard, see also Cole, J. S., "The Pulse Endopoler Coronary Artery Catheter", 56 Circulation, pp. 18-25 (July 1977). See also Martin et al, "An Ultrasonic Catheter Tip Instrument for Measuring Volume Blood Flow", IEEE Ultrasonics Conf. Proc. pp. 23-17 (1975);
Other investigators have suggested designs which are intended to image an obstruction within the lumen itself, i.e. an obstruction "in front" of an advancing catheter. U.S. Pat. No. 4,587,972 (Morantte, Jr.) discloses one such design. These approaches, however, fail to image a section of the vessel, and therefore do not provide critical information about the thickness of the vessel wall at a given location.
Ultrasound has also been used in vitro to characterize plaque in the human aorta. See B. Baizilai et al., "Quantitative ultrasonic characterization of nature of atherosclerotic plaques in human aorta", Circulation Research 60: 459 (1987). Using this technology in an in-vitro bath, it has been possible to distinguish fibrous, fatty, and calcific tissue.
Ultrasonic techniques have also been suggested for determining the cross-sectional area of various organs. U S Pat. Nos. 3,542,014 (Peonneau), 3,779,234 (Eggleton et al), 4,142,412 (McLeod et al), 4,237,729 (McLeod et al) 4,259,870 (McLeod et al) and 4,232,373 (Jackson et al) disclose various ultrasonic transducer arrangements for determining the cross-sectional area of internal organs. To some extent, such organs can be imaged using transducers placed on the body surface. It is possible to image the carotid arteries, the aorta and femoral arteries using these techniques. McPherson et al. have used a specialized high frequency transducer directly on the surface of the exposed human heart during cardiac surgery to provide a cross-sectional image of the coronary arteries. See D. McPherson et al. "Delineation of the Extend of Coronary Atherosclerosis by High Frequency Epicardial Echocardiography", New. E. J. of Med. 316, p. 304 (1987).
At a December, 1987 Contractors meeting of the Devices and Technology branch of the National Heart, Lung and Blood Institute, Dr. Charles Meyers reported on the performance of a feasibility study to determine if the details of the heart artery wall structure can be imaged with ultrasound. The study used a several millimeter diameter ceramic transducer on the end of a metal rod directed axially down the vessel center line. A 45.degree. elliptical mirror was mounted a short distance from the end of the ceramic transducer on a short piece of tubing so that the sound beam was directed radially into the vessel wall. The assembly was apparently a few inches long, so that it could be inserted into sections of cadaver arteries. Mechanical rotation of the transducer assembly was used to scan the sound beam in a radial direction, (plane position indicator scan) to build up a cross-sectional image of the artery wall. A number of these images indicated that many interior details of wall structure could be seen with short pulse excitation. When lesions were examined, the fatty areas showed up as echo free and calcium showed as strongly reflecting centers. The intrusion of both kinds of regions into the normal vessel wall was quite well demonstrated. In addition, fibrous tissue growth also was delineated, since the echoes appeared to occur as streaks parallel to the direction of the fibers. Dr. Meyers reported plans to build a flexible delivery device for the subject transducer. See Meyer, et al, "Feasibility of High-Resolution, Intravascular Ultrasonic Imaging Catheters", Radiology 168:113-116 (1988). Others have also reported on ultrasound imaging of vessels using intravascular catheters. See Hodgson et al, "Validation of a New Real Time Percutaneous Intravascular Ultrasound Imaging Catheter", American Heart Association Abstract (Nov. 14-17, 1988); Graham, "Utility of an Intravascular Ultrasound Imaging Device for Arterial Wall Definition and Atherectomy Guidance", American College of Cardiology Abstract (Mar. 19-23, 1989); Kophock et al, "Intraluminal Vascular Ultrasound: Dimensional and Morphologic Accuracy", Laser and Stent Therapy in Vascular Surgery--International Congress II (Feb. 10-15, 1989); Schwarten, et al, "Endovascular US: Adjunct to Percutaneous Atherectomy", Radiology Abstract 331; "Ultrasound Imaging Catheter Hailed For Diagnostic Accuracy", Cardiology World News, page 25 (July/August 1988); EndoSonics Cathscanner I System trade literature, EndoSonics Corp. Rancho Cordova, Calif. The potential for intravascular imaging was also recently reported in Medical World News, Jan. 9, 1989 at page 33. These catheter designs are said to comprise an ultrasound probe at the end of the catheter which emits a radial signal that produces a two-dimensional image of surrounding intra- and extravascular structures. A similar report on the progress of developing intravascular ultrasound imaging catheters as small as 0.8-1 mm appears in Moretti, M., "New Diagnostic Techniques Rely on Image Processing", Laser Focus/Electrooptics, pages 198-203 (April 1988).
U.S. Pat. Nos. 3,827,115 (Bom) and 3,938,502 (Bom) disclose a heart catheter with circumferentially arranged transducers for determining intraluminal diameter. Both Bom patents disclose a catheter useful with a hollow organ such as the heart, which catheter has elements on its distal end and is capable of transmitting and receiving ultrasonic waves. It has recently been reported that intravascular ultrasonic imaging devices can produce cross-sectional images. CVR & R 20-21 (June, 1988). Although details of the catheter construction were not reported, the catheter used in creating these images is described as comprising a 20-mHz ultrasound transducer of less than one mm in diameter on its tip, which is linked with a scanner for real-time display. Apparently the subject catheter utilizes piezoelectric crystals and is too large to image coronary arteries since the involved investigator, Dr. Paul G. Yock, reportedly desires to further miniaturize the device and reduce its cost "so that the instrument can be fabricated at reasonable cost". See also Mallery et al, "Intravascular Ultrasound Imaging Catheter Assessment of Normal and Atherosclerotic Arterial Wall Thickness" JACC Volume 11, No. 2, Abstract 22A (February, 1988), wherein a 1.4 mm diameter intravascular ultrasound imaging catheter with 5 20 mHz ultrasound transducers oriented radially at its tip is reported as showing promise as a method for accurately measuring normal and diseased arterial wall thickness. See also Bom et al., "Intra-Arterial Ultrasonic Imaging for Recanalization by Spark Erosion", Ultrasound in Med. & Biol., Vol. 14, No. 4, pp. 257-61 (1988). Bom reports that a previous 3.2 mm diameter 32-elements cylindrical catheter tip transducer was too large and that diminishing its size to an outer diameter of 2 mm "would be technologically difficult and would require an integrated circuit design for multiplexing, transmitting and receiving signals." The main reason not to follow this course is described by Bom as "the expected transmission pulse transient effect masking the near-by structure echoes". Accordingly Bom discloses a 20 MHz signal element construction in combination with an acoustic mirror utilized in a transducer element of one millimeter provided with an air backing and mounted onto a metal bar. Experience gained with these preliminary trials is said to have led to the decision to design a mechanically rotating catheter tip device that would provide cross-sectional two-dimensional images. The subject catheter is described as comprising a mirror mounted on the end of a flexible wire which can be rotated. The piezoelectric element is positioned over an air backing and comprises a tip of three "mutually isolated electrodes". Three electrode wires form an open cage for the echo signals and support the catheter tip.
As seen from the above, the recently suggested designs for intravascular probes are frequently bulky, difficult and expensive to manufacture, and unlikely to be miniaturized to the degree necessary to image most of the vessels of greatest importance. Accordingly, a need exists for a miniature intravascular, ultrasonic imaging catheter which is relatively easy to fabricate, and which can be used to generate high quality cross sectional images of vascular tissue, whether or not calcified.